HSV-1 Triggers an Antiviral Transcriptional Response during Viral Replication That Is Completely Abrogated in PKR−/− Cells

The activation of the innate immune response during HSV-1 infection stimulates several transcription factors, such as NF-kappa B and IRF3, which are critical regulators of IFN-beta expression. The released IFN-beta activates the ISGs, which encode antiviral effectors such as the PKR. We found that HSV-1 triggers an antiviral transcriptional response during viral replication by activating TBK1-IRF3-NF-kappa B network kinetically. In contrast, we reported that infected PKR-/- cells fail to activate the transcription of TBK1. Downstream, TBK1 was unable to activate the transcription of IRF3 and NF-kappa B. These data suggested that in PKR-/- cells, HSV-1 replication counteracts TBK1-IRF3-NF-kappa B network. In this scenario, a combined approach of gene knockout and gene silencing was used to determine how the lack of PKR facilitates HSV-1 replication. We reported that in HEp-2-infected cells, PKR can influence the TBK1-IRF3-NF-kappa B network, consequently interfering with viral replication. Otherwise, an abrogated PKR-mediated signaling sustains the HSV-1 replication. Our result allows us to add additional information on the complex HSV-host interaction network by reinforcing the concept of the PKR role in the innate response-related networks during HSV replication in an in vitro model.